Hematoma resolution as a target for intracerebral hemorrhage treatment: Role for peroxisome proliferator‐activated receptor γ in microglia/macrophages

Zhao, Xiurong; Sun, Guanghua; Zhang, Jie; Strong, Roger; Song, Wook; Gonzales, Nicole R.; Grotta, James C.; Aronowski, Jaroslaw

doi:10.1002/ana.21097

Cited by 346 publications

(427 citation statements)

References 39 publications

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“…Despite the detrimental effects of CD36 in an acute ischemic setting, CD36-dependent phagocytosis was associated with functional benefit in neonatal stroke [155]. Additionally, the clearing of red blood cells after hemorrhagic stroke was associated with increased CD36 expression and improved functional recovery [156]. This might be related to the role of CD36 in M2 phenotypic switching of mononuclear cells.…”

Section: Inflammation Versus Resolutionmentioning

confidence: 98%

Microglia and Monocyte-Derived Macrophages in Stroke

2016

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Historically, the brain has been considered an immune-privileged organ separated from the peripheral immune system by the blood-brain barrier. However, immune responses do occur in the brain in neurological conditions in which the integrity of the blood-brain barrier is compromised, exposing the brain to peripheral antigens and endogenous danger signals. While most of the associated pathological processes occur in the central nervous system, it is now clear that peripheral immune cells, especially mononuclear phagocytes, that infiltrate into the injury site play a key role in modulating the progression of primary brain injury development. As inflammation is a necessary and critical component for the subsequent injury resolution process, understanding the contribution of mononuclear phagocytes on the regulation of inflammatory responses may provide novel approaches for potential therapies. Furthermore, predisposed comorbid conditions at the time of stroke cause the alteration of stroke-induced immune and inflammatory responses and subsequently influence stroke outcome. In this review, we summarize a role for microglia and monocytes/macrophages in acute ischemic stroke in the context of normal and metabolically compromised conditions.

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Section: Inflammation Versus Resolutionmentioning

confidence: 98%

Microglia and Monocyte-Derived Macrophages in Stroke

2016

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“…Phagocytosis of several particulate Ags, such as RBC and apoptotic cells, is enhanced by PPAR-␥ agonists in microglia and macrophages (38,39,49). However, the ability of PPAR-␥ agonists to modulate bacterial phagocytosis by microglia has not yet been investigated.…”

Section: S Aureus Phagocytosis By Microglia Is Enhanced By Ciglitazonementioning

confidence: 99%

The Synthetic Peroxisome Proliferator-Activated Receptor-γ Agonist Ciglitazone Attenuates Neuroinflammation and Accelerates Encapsulation in Bacterial Brain Abscesses

Kielian

Syed

Liu

et al. 2008

The Journal of Immunology

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Brain abscesses result from a pyogenic parenchymal infection commonly initiated by Gram-positive bacteria such as Staphylococcus aureus. Although the host immune response elicited following infection is essential for effective bacterial containment, this response also contributes to the significant loss of brain parenchyma by necrosis that may be reduced by modulating the inflammatory response. Ciglitazone, a PPAR-γ agonist with anti-inflammatory properties, was evaluated for its ability to influence the course of brain abscess development when treatment was initiated 3 days following infection. Interestingly, abscess-associated bacterial burdens were significantly lower following ciglitazone administration, which could be explained, in part, by the finding that ciglitazone enhanced S. aureus phagocytosis by microglia. In addition, ciglitazone attenuated the expression of select inflammatory mediators during brain abscess development including inducible NO synthase, TNF-α, IL-1β, CXCL2, and CCL3. Unexpectedly, ciglitazone also accelerated brain abscess encapsulation, which was typified by the heightened expression of fibronectin and α-smooth muscle actin-positive myofibroblasts. Collectively, through its ability to attenuate excessive inflammation and accelerate abscess encapsulation, ciglitazone may effectively sequester brain abscesses and limit bacterial dissemination.

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“…We have also demonstrated that PPAR-γ agonists in vitro reduce production of proinflammatory mediators and free radicals produced during phagocytosis. Finally, PPAR-γ agonists in vivo demonstrate the ability to protect other brain cells from the secondary injury induced in a mouse model of ICH [102]. These data suggest that PPAR-γ in macrophages acts as an important factor in promoting hematoma absorption and protecting other brain cells from ICH-induced damage and may represent a promising therapeutic target in the management of ICH [103].…”

Section: Pharmacologic Hematoma Clearancementioning

confidence: 82%

“…Pre-clinical work in our laboratory demonstrates that peroxisome proliferators-activated receptor-gamma (PPAR-γ) agonists promote hematoma resolution, decrease neuronal damage, and improve functional recovery in a mouse model of ICH [102]. We have also demonstrated that PPAR-γ agonists in vitro reduce production of proinflammatory mediators and free radicals produced during phagocytosis.…”

Section: Pharmacologic Hematoma Clearancementioning

confidence: 93%

Treatment Targets in Intracerebral Hemorrhage

Sangha

Gonzales

2011

Neurotherapeutics

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Intracerebral hemorrhage (ICH) imparts a higher mortality and morbidity than ischemic stroke. The therapeutic interventions that are currently available focus mainly on supportive care and secondary prevention. There is a paucity of evidence to support any one acute intervention that improves functional outcome. This chapter highlights current treatment targets for ICH based on the pathophysiology of the disease.

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Hematoma resolution as a target for intracerebral hemorrhage treatment: Role for peroxisome proliferator‐activated receptor γ in microglia/macrophages

Abstract: PPARgamma in macrophages acts as an important factor in promoting hematoma absorption and protecting other brain cells from ICH-induced damage.

Cited by 346 publications

References 39 publications

Microglia and Monocyte-Derived Macrophages in Stroke

Microglia and Monocyte-Derived Macrophages in Stroke

The Synthetic Peroxisome Proliferator-Activated Receptor-γ Agonist Ciglitazone Attenuates Neuroinflammation and Accelerates Encapsulation in Bacterial Brain Abscesses

Treatment Targets in Intracerebral Hemorrhage

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